Spontaneous abdominal bleeding associated with SARS-CoV-2 infection: causality or coincidence?

Authors present 6 cases of abdominal bleeding associated with COVID-19, representing 1.35% of all hospitalized COVID-19 patients and hypothesize that there could be, although not very frequently, a relationship between SARS-CoV2 and bleeding. They excluded a side effect of the low molecular weight heparin therapy that all patients underwent during the course of the disease or other possible causes. Alterations of the coagulation state or a weakness of the vascular wall due toa presumed endotheliitis SARS-CoV-2 infection induced, are hypothesized by the authors. Investigation and follow-up for possible hemorrhagic problems in patients with COVID-19 is recommended. In particular, clinicians should be vigilant about retroperitoneal hemorrhage in COVID-19 patients. In addition to the fact that these patients are being treated with anticoagulants, anemia and abdominal pain are the signs that should lead us to suspect this type of haemorrhage. More studies are needed to understand if COVID-19 can be directly associated with bleeding. (www.actabiomedica.it)

Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice.

Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95%CI 1.10-2.92 per 1-log(10) increase, P=0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P<0.001) as independent predictors of HIV-1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice.

Mesalazine-induced multi-organ hypersensitivity.

Mesalazine therapy for ulcerative colitis has been reported to be effective and safe. Rare cases of mesalazine-induced renal, pancreatic, myo-pericardial, pleuro-pulmonary and haematological toxicity have been described separately. We report a case characterized by the simultaneous presence of fever, pericarditis, peripheral eosinophilia, eosinophilic pneumonia, anaemia and haematuria (together with proteinuria and leukocyturia) due to mesalazine treatment in a patient with ulcerative colitis. No clinical response had been obtained with corticosteroids and various antibacterial agents. When mesalazine treatment was suspended, all symptoms rapidly and totally disappeared, confirming the direct responsibility of this drug in causing these adverse events. We conclude that mesalazine can induce multi-organ hypersensitivity, which must always be considered as a possible adverse effect during treatment with this drug. To resolve this adverse event it is essential to discontinue mesalazine treatment.

Divergent distribution of HIV-1 drug-resistant variants on and off antiretroviral therapy.

OBJECTIVE: To investigate the distribution of drug-resistant HIV-1 variants in plasma RNA and peripheral blood monuclear cell (PBMC) DNA at treatment failure while on therapy and after stopping therapy. DESIGN: Fifty-eight patients failing their first highly active antiretroviral treatment while on therapy and 50 patients after a median of 18.6 weeks after treatment interruption following multiple treatment failures were analysed. METHODS: Paired plasma HIV-1 RNA and PBMC HIV-1 DNA were used for genotypic antiretroviral resistance testing. Drug resistance was computed by using the Stanford on-line genotype interpretation system. RESULTS: The extent of drug resistance was larger in plasma RNA than in PBMC DNA in the on-therapy group (P=0.004) and in PBMC DNA than in plasma RNA in the off-therapy group (P=0.04). Interpretation of genotype based on PBMC DNA and plasma RNA in the on-therapy and in the off-therapy group would have missed detection of resistance to one or more drugs in 21 and 22% of the patients, respectively, compared to interpretation based on the other blood compartment. In a subset of 27 patients for whom a sample before stopping therapy was available, there was a significant decrease in the number of RNA (mean 8.1 to 5.3, P=0.004), but not DNA (mean 6.8 to 5.7, P=0.143), resistance mutations following treatment interruption. CONCLUSION: While plasma RNA is the material of choice for early detection of drug resistance while on therapy, analysis of PBMC DNA may additionally support and possibly improve sensitivity of resistance testing in the absence of therapy.

Darunavir-based dual therapy in HIV experienced patients.

BACKGROUND: We assessed the virological response of DRV/r-based dual therapy in drug-experienced patients included in the Italian antiretroviral resistance database (ARCA). MATERIALS AND METHODS: Patients included in the study were treated with DRV/r in association with raltegravir (RAL), etravirine (ETV) or maraviroc (MAR) following treatment failure(s) and with a resistance test and at least one follow-up visit available. Observation was censored at last visit under dual therapy and survival analysis and proportional hazard models were used, taking virological failure (confirmed >50 c/mL HIV-RNA) as the end-point. RESULTS: Of the total 221 patients included, 149 (67.4%) started DRV/r with RAL, 45 (20.4%) with ETV, 27 (12.2%) with MAR. Patients characteristics at the start of dual regimen were as follows: mean number of previous regimens, nine (IQR: 5-13); non-B subtype, 17 (7.7%); median CD4 count, 347 (IQR: 246-544); undetectable viral load, 74 (33.5%). Full DRV/r resistance was detected in one (0.5%, HIV-DB interpretation system), 13 (5.9%, ANRS) and 17 patients (7.7%, Rega). 69 virological failures (31.2%) were observed during follow-up. At survival analysis, the overall proportion of failure was 29.2% at one year and 33.8% at two years. The proportion of failure was lower in patients starting with undetectable versus detectable viral load (13.3% and 25.2% versus 37.4% and 38.8% at one and two years, respectively, p=0.001 for both analyses) and in patients treated with DRV 600 BID versus 800 QD (HR: 0, 56; 95% CI 0.31-0.99; p<0.05). By regimen, patients treated with DRV/r-RAL showed a non-significant lower proportion of failure (27.7% at one year, 32.0% at two years) if compared with DRV/r-MAR (35.9%, 47.1%) and DRV/r-ETV (34.1%, 34.1% at one and two years). In the adjusted proportional model, no significant difference among the three regimens was detected. A significant lower risk of failure was associated with higher overall GSS (HIV-DB HR: 0.53, 95% CI 0.32-0.88, p=0.014; Rega 0.60, 0.40-0.88, p<0.01; ANRS 0.55, 0.34-0.90, p=0.017), while a higher risk of failure was associated with detectable HIV-RNA (3.02, 1.70-5.72, p<0.001). CONCLUSIONS: Among experienced patients, the best candidates to dual-therapy regimens including DRV/r are those with undetectable viral load and higher GSS. The association with RAL is the most commonly used but no clear advantage with respect to ETV or MAR was observed in our dataset, possibly due to the limited sample size.